Infertility
Conditions
Brief summary
This randomized trial was designed as non-inferiority trial aiming to compare ongoing pregnancy rates following LPS with 600 mg/day vs 800 mg/day vaginal VMP. All patients will undergo an artificial cycle frozen embryo transfer (AC-FET) with transdermal estradiol 6mg/day Patients undergoing an artificial cycle FET will start estrogen priming with transdermal estradiol 6mg/day (Estrogel®) on cycle D1-D3. Following 10-12 days of estrogen priming, patients will be randomized to luteal phase support with a standard formulation (200mg tid, Utrogestan®) or a new formulation (400mg bid) VMP. All patients will undergo a serum P measurement on the day before embryo transfer (ET). Patients with P\<10 ng/ml will receive a supplement of oral micronized progesterone 300mg, while patients with P≥10ng/ml will maintain the previous luteal phase support (LPS) protocol
Interventions
DRUGVaginal progesterone 600mg daily
If endometrial thickness (ETH) ≥7 mm and follicle dominance/ultrasound (US) signs of ovulation P levels are measured: if P ≤1.5 patients start LPS, else cycle is cancelled. If ETH \<7mm and no follicle dominance: estradiol dose is increased to 9mg/day and new US is performed up to 4 days after. If persistent thin endometrium after dose increase, cycle is cancelled. 24-48h pre ET, E2 and P are measured. in the morning, pre VMP dose, or at least 6h after last progesterone dose. If progesterone \<10ng/ml, additional 300mg daily oral micronized progesterone is administered on the day of the ET and maintained until 10 weeks pregnancy or up to menses or up to negative pregnancy test 10 days after ET. ET will be performed with available blastocysts 6 days after start of LPS. 3-5 days, after ET, a blood test for P measurement will be performed in the morning, before VMP dose, or at least 6h after last progesterone dose. 10 days after ET, the last P test will be done with pregnancy test.
DRUGVaginal progesterone 800mg daily
If endometrial thickness (ETH) ≥7 mm and follicle dominance/ultrasound (US) signs of ovulation P levels are measured: if P ≤1.5 patients start LPS, else cycle is cancelled. If ETH \<7mm and no follicle dominance: estradiol dose is increased to 9mg/day and new US is performed up to 4 days after. If persistent thin endometrium after dose increase, cycle is cancelled. 24-48h pre ET, E2 and P are measured. in the morning, pre VMP dose, or at least 6h after last progesterone dose. If progesterone \<10ng/ml, additional 300mg daily oral micronized progesterone is administered on the day of the ET and maintained until 10 weeks pregnancy or up to menses or up to negative pregnancy test 10 days after ET. ET will be performed with available blastocysts 6 days after start of LPS. 3-5 days, after ET, a blood test for P measurement will be performed in the morning, before VMP dose, or at least 6h after last progesterone dose. 10 days after ET, the last P test will be done with pregnancy test.
Sponsors
Fundación Santiago Dexeus Font
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Endometrial preparation with hormone replacement therapy * Age 18-43 years following an autologous IVF cycle (with or without preimplantation genetic testing for aneuploidy) * Age \< 50 years following an egg donation cycle * BMI \> 18 and \< 30 kg/m2 * blastocyst embryo transfer * Willing to participate in the study * Able to come to the Center to comply with the procedures of the study: blood tests, appointments and drug dispensation. Exlusion Criteria: * • Uterine diseases (e.g. submucosal fibroids, polyps, previously diagnosed Müllerian abnormalities) * Hydrosalpinx * Recurrent pregnancy loss (≥ 3 previous miscarriages) * Recurrent implantation failure (≥ 3 previously failed embryo transfers of good-quality blastocysts) * Allergy to study medication * Pregnancy or lactation * Contraindication for hormonal treatment * Personalized initiation of exogenous progesterone according to a previous endometrial receptivity assay test * Recent history of severe disease requiring regular treatment (clinically significant concurrent medical condition that could compromise subject safety or interfere with the trial assessment).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing pregnancy rate | 7-9 weeks after embryo transfer | A positive heart beat at ultrasound after 11-13 weeks of gestation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Implantation rate | 3-4 weeks after embryo transfer | Number of gestational sacs over total embryo transfered |
| Biochemical pregnancy rate | 10 to 12 days after embryo transfer | positive beta-human chorionic gonadotropin (hCG) |
| Clinical pregnancy rate | 3-4 weeks after embryo transfer | A positive heart beat at ultrasound |
| Miscarriage rate | before completion of 12 weeks of gestation | any spontaneous abortion that occurred after confirmation of clinical pregnancy |
| Frequency of adverse events | Until 15 days after the end of treatment with progesterone | — |
Countries
Spain
Contacts
CONTACTNikolaos P Polyzos, MD, PhD
CONTACTIgnacio Rodríguez, MSc
STUDY_CHAIRNikolaos P Polyzos, MD, PhD
Service of Reproductive Medicine Dexeus University Hospital
PRINCIPAL_INVESTIGATORNoemie Sachs-Guedj, MD
Service of Reproductive Medicine Dexeus University Hospital
Outcome results
None listed